Nutritional composition with health promoting action contaning oligosaccharides

ABSTRACT

A nutritional composition having beneficial effect in the gastrointestinal tract, especially an anti-adhesion effect on pathogenic micro-organisms and a bifidogenic effect, contains non-digestible oligosaccharides, said oligosaccharides comprising, per daily dosage, 0.3-10 g of oligosaccharides containing at least one terminal arabinose unit. The nutritional composition may furhermore comprise 0.5-10 g of other non-digestible oligosaccharides selected from fructo-oligosaccharides, galacto-oligosaccharides, xylo-oligosaccharides and manno-oligosaccharides. The arabino-oligosaccharides can be obtained conveniently by controlled hydrolysis of arabinose-containing polysaccharides irom natural (vegetable) origin.

[0001] The present invention relates to nutritional compositions withhealth-promoting action, in particular having a bifidogenic effect andhaving an anti-adhesive effect on pathogenic micro-organisms to theintestinal wall.

[0002] More specifically, in a first aspect, the invention relates tosuch a nutritional composition containing at least one oligosaccharidehaving at least one terminal arabinose unit.

[0003] As used herein, an oligosaccharide means a saccharide consistingof at least two, up to 20 glycosidically linked monosaccharide units,i.e. having a degree of polymerisation (DP) of 2-20. Saccharides of morethan 20 units are referred to herein as polysaccharides. Theoligosaccharides are poorly or non-digestible, i.e. are not readilyconverted to caloric substrates by the mammalian digestive enzymes.

[0004] The use of arabinose-containing polysaccharides in food productsis known. GB 1,072,029 discloses the use of arabinogalactans having amolecular weight in the range of 70-95 kDa (DP 450-600) as a bulksweetener combined with an artificial sweetener. According to U.S. Pat.No. 6,004,610, such arabinogalactans can be used together withhydrolysed guar gum as a dietary fibre in beverages, because of theirlow viscosity. WO 00/08948 (DE-198,36339) describes the use of acombination of an oligosaccharide (up to a hexasaccharide) and apolysaccharide (from a heptasaccharide upwards) for promoting flora ofthe human large intestine. Arabinans are mentioned as one of manypossible polysaccharides.

[0005] The oligosaccharides to be used according to the invention haveat least one terminal arabinose unit, i.e. at least one arabinose unitwhich is linked to the remainder of the oligosaccharide molecule by one(glycosidic) bond. These terminal arabinose units may be located at theend of the main chain of the oligosaccharide, whether it is a reducingend (having a free hemiacetal function) or a non-reducing end, or both,but they may also be located at the end of side chains to the main chainor be directly bound to the main chain by a single bond. In the presentdescription, the oligosaccharides having one or more terminal arabinoseunits are also referred to as “arabino-oligosaccharides”.

[0006] In its simplest form, an arabino-oligosaccharide of the inventionis a dimer of two saccharide residues substituted, at least one of whichis an L-arabinose residue. The other saccharide residue may be chosenfrom all saccharide residues, and in particular those saccharideresidues that are present in naturally occurring saccharide polymers,such as galactose, arabinose, mannose and xylose. Most preferably theother saccharide is arabinose or galactose. Similarly, intrisaccharides, one or both of the terminal saccharide units arearabinose residue, while the remaining ones can be galactose, xylose,mannose etc., and the central arabinose can also be arabinose.

[0007] Longer arabino-oligosaccharides may be straight-chain(unbranched) or preferably branched oligosaccharides composed of anycombination of saccharide units, as long as at least one terminal one isarabinose. The oligosaccharides may be linked by α-links, at 1,2-, 1,3-,1,4- and/or (if applicable) 1,5- or 1,6- positions and, if ketoses areinvolved, 2,1-, 2,4-, 2,6- positions etc. L-Arabinose units in thearabino-oligosaccharides are usually in their furanoside form, but mayalso be in the pyranoside form. They are predominantly α-1,3- or α-1,5linked. The number of L-arabinose residues present in thearabino-oligosaccharides may vary, provided that at least one arabinoseresidue, preferably at least two arabinose units, are present on atleast one end of the oligosaccharide chain. Thus, only one (i.e. the atleast one terminal residue), several or essentially all of thesaccharide residues that form the backbone of the saccharide oligomermay be substituted with an L-arabinose residue. The backbone itself mayconsist of arabinose units or other units (galactoses, xyloses etc.).

[0008] The oligosaccharide units usually contain aldoses (and ketoses)only, but may also contain uronic acid, methylated or acylated or othercommonly derivatised units.

[0009] The arabino-oligosaccharide may be a pure, exactly definedoligosaccharide or, more comnmonly a mixture of oligosaccharides withvarying chain length and possibly also with varying branching patternsand/or varying saccharide composition. The arabino-oligosaccharides arepreferably of natural origin, either directly isolated from theirnatural source, or isolated and hydrolysed or synthesised by chainlengthening. Hydrolysis may be effected chemically (acid) orenzymatically (glycanases) as described below, and synthesis istypically effected enzymatically (transferases).

[0010] Some suitable sources of such naturally occurring insolublepolymers include sugar beet extract, which contains mainly lineararabinans, cereal fibre, e.g. of wheat and barley, which containsbranched arabino-xylo-saccharides (xylan chains which arabinose andother side units), and apple, potato and soybean fibre, which containbranched arabinogalactans of various types. They may also originate fromarabinose-containing gums, such as gum arabic, tragacanth (the bassorinfraction thereof), gum ghatti etc.

[0011] The presence of one or more arabino-saccharides in a sample—suchas the nutritional compositions of the invention and/or the hydrolysatesmentioned below—can be assayed using analytical techniques known per se,such as high performance anion-exchange chromatography (HPAEC), andtheir amounts can be determined e.g. by preparative gel filtrationfollowed by trifluoroacetic acid hydrolysis and HPAEC.

[0012] The nutritional composition of the invention may contain one orseveral different (types of) arabino-oligosaccharides. When thenutritional composition of the invention contains several differentarabino-oligosaccharides, these may differ in their degree ofpolymerisation (DP, the total number of saccharide residues in theoligosaccharide chain); in the number and/or the position of theL-arabinose residues present on their oligosaccharide chain; in the(types of) the saccharide residues that form the oligosaccharide chain,the relative amounts thereof and/or the order thereof; and/or in anycombination thereof. Also, the arabino-oligosaccharides present in thenutritional composition of the invention may differ in the manner inwhich they were obtained and/or in the starting material from which theywere obtained, e.g. as further described below.

[0013] In the present invention, the arabino-oligosaccharides arepreferably provided and incorporated into the nutritional composition inthe formn of a hydrolysate containing at least onearabino-oligosaccharide as defmed above. Such hydrolysates form afurther aspect of the invention. Preferably, such hydrolysates areobtained by hydrolysis of a starting material containing one or moreL-arabinose-substituted polymers, preferably from natural origin. Ofcourse, mixtures of such naturally occurring polymers and/or of suchnaturally available starting materials may also be used.

[0014] Generally, the hydrolysates of the invention will contain atleast one oligomer, and usually several different oligomers, dependingupon the starting material chosen, the way in which the startingmaterial has been hydrolysed, as well as the further processing,separation and/or purification steps applied after hydrolysis (if any).

[0015] Furthermore, besides the desired arabinose-terminated oligomers,the hydrolysates of the invention may also contain amounts of arabinosemonomers and other saccharide monomers. They may also contain amounts ofarabinose-substituted saccharide polymers with a degree ofpolymerisation (chain length) of more than 20. Again, this will dependupon the starting material chosen, the way in which the startingmaterial has been hydrolysed, as well as the further processing,separation and/or purification steps applied after the hydrolysis, ifany.

[0016] According to the invention, it has been found that, in thenutritional compositions of the invention, the presence of certainamounts of monomers of polymers (including insoluble polymers) will notessentially influence (e.g. detract from) the health promoting action ofthe L-arabinose substituted oligomers of the invention, and alsootherwise can be tolerated. However, preferably, the amount of oligomersin the hydrolysates used in the nutritional compositions of theinvention is at least 5%, preferably at least 20%, based upon the totalamount of oligomers, monomers and polymers (including insolublepolymers) present in the hydrolysates.

[0017] Thus, the hydrolysates that are incorporated into the nutritionalcompositions of the invention may contain, as far asarabinose-containing carbohydrates are concerned (weight ratios): 0-50%of monomers, 10-100% of oligomers (2- to 20-mers) and 0-70% of polymers(>20-mers). Preferably the ratios are 2-40% of monomers, 20-80% ofarabinose-containing oligomers, 2-40% of other oligomers, and 10-60% ofpolymers. Most preferably, the ratios are 35-75% of arabinose-containingoligomers, 5-30% of other non-digestible oligomers, 5-30% of monomers,and 15-35% of non-digestible polymers.

[0018] The hydrolysis of the starting polymers—i.e. to provide the abovehydrolysates—may be carried out in any manner known per se, dependinguxpon the starting material used and the desired hydrolysate. Acidhydrolysis and enzymatic hydrolysis are preferred, with enzymatichydrolysis being particularly preferred. Suitable conditions for acidhydrolysis include the use of aqueous media containing acids such ashydrochloric acid, sulphuric acid, phosphoric acid, an organic acid orpolymeric or immobilised acids (acid resin) under usual conditions.

[0019] For enzymatic hydrolysis, any enzyme or enzyme combinationsuitable for degrading the starting polymers may be used. Preferably,these are endo-enzymes, and suitable examples and sources thereof willbe clear to the skilled person. Enzymatic synthesis can be performedwith transferase, i.e. enzymes capable of transferring an arabinoseresidue to a mono- or oligosaccharide.

[0020] Suitable conditions for enzymatic hydrolysis will depend upon thestarting material and the enzyme used. Preferably, a pH and atemperature near the optimum pH and temperature of the enzyme is used.Suitable conditions may for instance comprise the use of purifiedendogalactanase of 1 μg/ml in an aqueous substrate solution at a pHbetween 4.5 and 6, at a temperature of about 30° C. for 30 minutes to 3hours at a concentration of starting arabinogalactan of 0.5-20 wt. %. Aswill be clear to the skilled person, the starting materials, the enzymesused, the hydrolysis conditions and the optional further processingsteps most preferably are chosen such that the resulting hydrolysate isstill acceptable for use in the nutritional compositions of theinvention. Usually, this will involve the use of starting materials,enzymes etc. acceptable for use in food applications, e.g. having theGRAS status.

[0021] Generally, the hydrolysis is allowed to proceed until thehydrolysate obtained contains at least 10%, preferably at least 20%,most preferably at least 50% arabinose-containing oligomers. Theprogress of the hydrolysis may be followed using any suitable method,which will usually involve determining the amount of the oligomersformed, the amount of monomers formed, and/or the amount of polymersremaining. Suitable techniques, such as chromatography techniques, willbe clear to the skilled person. The arabinose-containing startingpolymers may be used as such, or may be purified so as to increase theyield of desired product. Such pre-treatment may include chemicalextraction (sodium hydroxide solution) or physical extraction(extrusion).

[0022] For instance, for the degradation of naturally occurring polymersmentioned below, and for the transfer synthesis, respectively, thefollowing enzymes be used: Starting material Enzyme Oligomer arabinanendo-arabinase arabino-oligosaccharides arabinoxylan endo-xylanasearabinoxylo- oligosaccharides arabinogalactan endo-galactanasearabinogalacto- oligosaccharides arabinobiose arabinofuranohydrolasearabinotriose and higher homologues

[0023] The hydrolysates obtained after the hydrolysis may beincorporated as such into the nutritional compositions of the invention,or after further processing/purification steps, for instance to quenchthe hydrolysis reaction (e.g. to inactivate the enzyme(s) and/or toincrease the pH), to remove components of the hydrolysis mixture such assalts and/or the enzymes used; to remove byproducts of the hydrolysisreaction; and/or the reduce the amount of monomers or the amount ofsoluble or insoluble polymers. This may be carried out using anypurification and/or processing techniques known per se, includingneutralisation, precipitation, filtration, dialysis, ultrafiltration, ora suitable combination of such steps. These steps preferably result in ahydrolysate as described above for incorporation in the nutritionalcompositions of the invention.

[0024] Also, a nutritional composition of the invention may contain acombination of such hydrolysates, i.e. obtained from different startingmaterials, using different hydrolysis conditions (e.g. enzymes usedand/or fmal degree of hydrolysis) and/or different furtherpurification/processing steps.

[0025] Thus, in a further aspect, the invention relates to a method forpreparing a hydrolysate containing at least one L-arabinose substitutedoligosaccharide, said method comprising hydrolysing one or moreL-arabinose substituted polymers and optionally one or more furtherprocessing steps known per se.

[0026] The invention is based on the discovery that the oligomericarabans have a health-promoting action, in particular with respect tothe prevention and/or treatment of disorders of the gastrointestinaltract. In particular, it has been found that thearabino-oligosaccharides can prevent and/or reduce adhesion ortranslocation of undesired micro-organisms to the intestinal wall, andalso have a “bifidogenic” effect, by which is meant that they canpromote a healthy flora in the gastrointestinal tract, which in infantsmakes it more similar to the flora of breast-fed infants and/or can beused to prevent and/or treat any disturbance in the naturally occurringflora in the gastrointestinal tract. These effects are especiallybeneficial in clinical patients and in newborns. Also, the productsinduce an enhanced immune function and an improved absorption ofminerals like calcium and magnesium, which is beneficial to menopausalwoman, elderly persons, and patients suffering from a disturbedintestinal function.

[0027] The compositions of the invention may provide theirhealth-promoting action throughout the entire small and large intestineand/or one or more parts thereof, including the duodenum, jejunum, ileumand colon. Similarly, the compositions of the invention may also providetheir anti-adhesion and/or their bifidogenic effect throughout theentire intestinal tract and/or parts thereof, which may be the same ordifferent parts.

[0028] For this purpose, the nutritional compositions of the inventionmay contain several different oligomers, which may provide for healthpromoting action in different parts of the gastrointestinal tract. Also,the nutritional compositions of the invention may contain severaldifferent oligomers, one or more of which provide for ain anti-adhesioneffect and one or more of which provide for a bifidogenic effect. Also,nutritional compositions of the invention may contain differentoligomers (e.g. with different degrees of hydrolysis) so as to providefor an anti-adhesion effect in different parts of the gastrointestinaltract, and/or several different oligomers (e.g. with different degreesof hydrolysis) as to provide for a bifidogenic effect in different partsof the gastrointestinal tract.

[0029] In this way, oral administration of a nutritional composition ofthe invention containing several different oligomers, suitably chosen,can produce the desired health-promoting action in several or inessentially all parts of the gastrointestinal tract simultaneously.Also, by oral administration of such a composition, both ananti-adhesion and a bifidogenic effect can be obtained simultaneously,in one, several or essentially all parts of the gastrointestinal tract,which may be the same of different. Also, by using a combination ofseveral different oligomers, a synergistic effect may be obtained.

[0030] According to one preferred aspect, the nutritional compositionsof the invention provide their anti-adhesion effect in the smallintestine and/or provide their bifidogenic effect in the largeintestine. Generally, for an anti-adhesion effect, small linear andbranched oligomers, preferably with a degree of polymerisation (DP) of2-10 are most suited. For a bifidogenic effect, oligomers which arebranched and have a DP of up to 20 are most suited.

[0031] Generally, to obtain the health promoting action effect of theinvention, the oligomers will usually be administered to an adult in anamount ranging between 0.01 and 0.5 g per kg body weight per day; and toan infant in an amount ranging between 0.02 and 1.0 g per kg body weightper day. These amounts of oligomers may be administered as a single doseper day or as several doses per day, with 1-6, in particular 1-3 dosesper day being preferred.

[0032] More specifically, to obtain the anti-adhesion effect of theinvention, the arabino-oligosaccharides will usually be administered toan adult in an amount ranging from 0.01 to 0.2 g per kg body weight perday; and to an infant in an amount ranging from 0.02 to 0.4 g per kgbody weight per day; again as a single or as several doses per day.

[0033] To obtain the bifidogenic effect of the invention, the oligomerswill usually be administered to an adult in an amount between 0.1 and0.5 g per kg body weight per day; and to an infant in an amount between0.2 and 1.0 g per kg body weight per day; also as a single or as severaldoses per day.

[0034] From the above, it will be clear that—as the amount ofarabino-oligosaccharides that is usually administered to obtain thebifidogenic effect is larger than the amount usually administered toobtain the anti-adhesion effect—administering thearabino-oligosaccharides to obtain the bifidogenic effect will usuallyalso result in a anti-adhesion effect, depending upon the oligomerspresent.

[0035] The adninistration of the nutritional compositions of theinvention may be continued until the desired health promoting action isobtained and/or—when administered as prophylactics—until the individualis no longer exposed to conditions which require (additional) protectionagainst disorders of the gastrointestinal tract.

[0036] The nutritional composition of the invention may be in any formsuitable for human administration, and in particular suitable foradministration to any part of the gastrointestinal tract. Usually, andpreferably, this will involve (compositions suitable for) oraladministration, although for instance administration into the gut—suchas through a tube or catheter—also forms part of the invention.

[0037] In particular, the nutritional composition may be in the form ofa food supplement or in the form of a complete food which is ready forconsumption, such as a total food or infant formula.

[0038] When the composition of the invention is in the form of a foodsupplement, it can be in a form for separate administration, such as acapsule, a tablet, a powder, a sachet, a liquid composition (e.g.droplets) or a similar form, containing preferably a unit dose ofoligomers of the invention. Such a supplement may further comprise oneor more adjuvants, carriers or excipients suitable for use in foodsupplements, as well as one or more of the further components and/oradditives described below.

[0039] The food supplement may also be in the form of a powder, a liquidcomposition (e.g. droplets) or a similar form, which is added to ormixed with a suitable food (composition) or a suitable liquid or solidcarrier, for the preparation of a food or drink which is ready forconsumption. For instance, the food supplement may be in the form of apowder which can be mixed with, and/or reconstituted with, water, milk,fruit juice, toddler drinks, oral rehydration solution (to provide aso-called ORS drink), etc. It can also be in the form of a powder orliquid that can be mixed with solid foods or with foods with ahigh-water-content, such as fermented foods, for example yoghurt.

[0040] A food supplement according to the invention preferably containsthe non-digestible arabinose-containing oligosaccharides (1) togetherwith non-digestible polysaccharides (3) (whether or not containingarabinose units), optionally other non-digestible oligosaccharides (2)and digestible carbohydrates (4), such as glucose, fructose, and/ormalto-dextrins, in a weight ratio of (1)+(2)+(3) to (4) of 1:5 to 24:1.The amount of (1) is 1-90% of the total dry weight of the supplement,preferably 5-40%, the amount of (2) is 0-50%, preferably 2-25%, theamount of (3) is 2-50%, preferably 5-30%, and the amount of (4) is4-80%, preferably 10-50%. The remainder, if any, may be vitamins,minerals, proteins, colorants, preservatives and the like.

[0041] The nutritional compositions of the invention can also be in theform of a solid, semi-solid or liquid food which is ready forconsumption. Such a food will usually comprise—besides the one or moreoligomers of the invention—a food or food base known per se, and can forinstance be prepared by

[0042] adding a food supplement as described above to a food or foodbase known per se;

[0043] adding one or more oligomers of the invention to a food or foodbase known per se; and/or

[0044] incorporating one or more oligomers of the invention to a food orfood base known per se during the preparation thereof.

[0045] As such, the nutritional compositions in the invention can befoods for oral consumption, for instance a total food or an infantformula. They can also be foods for administration by tube or catheterinto the stomach, e.g. by tube or catheter.

[0046] The nutritional composition of the invention, whether in the formof a food for consumption or a food supplement, can further comprise alldesired components and/or additives for use in foods or foodsupplements, including but not limited to flavours, colourings,preservatives, sugar, etc., as long as these do not interfere (too much)with the desired health promoting action of the oligomers. Thecomposition can contain one or more peptides and/or proteins, lipids,carbohydrates, vitamins, minerals and trace elements, in usual amounts.

[0047] A complete food according to the invention preferably comprisesproteins (4-35%, preferably 7-25%), lipids (4-40%, preferably 7-35%),digestible carbohydrates (30-90%, preferably 35-75%), in addition to0.07-6%, preferably 0.2-4% of non-digestible arabinose-containingoligosaccharides. The balance up to 100% (all percentages by weight) maybe other non-digestible carbohydrates, e.g. in a proportion of 0-10%,preferably 0.1-5%, at least half of which preferentially consists ofoligosaccharides. Where the complete food is a tube-feeding, the amountof non-digestible arabinose-containing oligosaccharides is preferably0.07-2.5%, in particular 0.2-2%. In an infant formula, the amount ofnon-digestible arabinose-containing oligosaccharides is preferablyhigher, i.e. 0.15-6%, in particular 0.4-4%.

[0048] The composition of the invention can also contain one or moreadditional substances that inhibit bacterial adhesion to the epithelialwall of the gastrointestinal tract, including mannans, galacturonic acidoligomers, preferably of natural origin, as a result of which asynergistic effect may be obtained.

[0049] The compositions can and preferably do also contain prebiotics,as well as prebiotic compounds, in particular fibres and proteins.Fibres in particular include soluble and insoluble non-digestiblepolysaccharides, such as non-starch polysaccharides (of the cellulose,hemicellulose and other types), resistant starch, gums etc. It isparticularly preferred that the compositions of the invention compriseother non-digestible oligosaccharides, which are usually soluble. Theseinclude (trans-)galacto-oligosaccharides (TOS or GOS),fructo-oligosaccharides (FOS), xylo-oligosaccharides (XOS) andmanno-oligosaccharides. These other oligosaccharides are preferablyobtained from natural sources, either by direct extraction, e.g. in thecase of inulin (FOS), or by hydrolysis of suitable polysaccharide orpolysaccharide mixture, e.g. in the case of inulin and levan (FOS),galactans and galactomannans (TOS), and xylans and other hemicelluloseconstituents (XOS) or by enzymatic synthesis using the appropriatetransferases, e.g. in the case of FOS and TOS.

[0050] These other oligosaccharides may be added as such, especially ifthey are obtained by direct extraction or synthesis (FOS or TOS) or theymay be co-hydrolysed with the arabino-polysaccharides to obtain anoligosaccharide fraction containing both arabino-oligosaccharides of theinvention and other oligosaccharides, e.g. xylo- and/orgalacto-oligosaccharides. These may (further) help to maintain and/orrestore the intestinal flora, which again may result in a synergisticeffect. The amounts of other oligosaccharides may vary, e.g. from 10% to400% with respect to the total amount of non-digestibleoligosaccharides, especially in a ratio of arabino-oligosaccharides(AOS) to other oligosaccharides between 1:3 and 3:1.

[0051] The compositions may advantageously also contain probioticorganisms such as bifidobacteria, lactobacilli and other lactic acidbacteria, e.g. at levels of at least 107 viable micro-organisms perdaily dose per individual.

[0052] The compositions of the invention may also contain antibodiessuch as immuno-globulins that act specifically against the pathogenicmicro-organisms, more specifically against enterotoxigenic E. coilstrains, rotaviusses, Clostridia, Salmonella and/or Campylobacterspecies. These immunoglobulins are used in amounts of at least 20 μg per100 g of the composition. The compositions can also contain at least 2mg/100 g of the composition sialylated compounds, and at least 2 mg/100g product of a bactericidal compound, such as preferably lactoferrin.

[0053] Also, the compositions of the invention may contain otherhealth-promoting components known per se, such as medicaments, etc. Inparticular, the compositions may contain compounds which have abeneficial influence on the gastro-intestinal tract, such asglutamine/glutamate or precursors thereof, which provide fuel for thecells of the gastrointestinal wall. Again, by the use of such acombination, a synergistic effect may be obtained.

[0054] The amount of the one or more oligomers described above that ispresent in a nutritional composition of the invention will usuallydepend upon—inter alia—the oligomers used, the form of the composition(e.g. as a total food or as a food supplement), the intended healthpromoting effect (e.g. adhesion inhibiting and/or bifidogenic), and thenumber of doses per day to be administered. Generally, the amount willbe such that it allows easy administration of the oligomers in the dailyamounts mentioned above, e.g. as a single dose or as several doses perday.

[0055] Amounts to be administered are given below with reference to adaily dosage, unless indicated otherwise. A daily dosage for an adult istaken as corresponding to an energy intake of 2000 kcal/day, or about 25kcal per kg body weight per day. Thus, an amount given as a daflydosage, where complete foods are concerned, means an amount per 2000kcal energy for an adult. For an infant, the energy intake is usuallyhigher e.g. about 50 kcal per kg body weight per day. For foodsupplements, the amount are naturally higher: if the supplement containsenergy components, such as carbohydrates, the amount per daily dosagemay be e.g. the amount per 200 or per 400 kcal energy. The amounts givenmay also refer to the total weight of the nutritional composition asgiven below and in the appending claims.

[0056] Usually, a nutritional composition of the invention will containa unit dose of the oligomers and/or a predetermined amount ofhydrolysate. For instance, a food supplement of the invention maycontain a total of 0.3 to 10.0 g of arabinose-containing oligomers,and/or a total of 2.5 to 50 g of hydrolysate of the invention. Preferredamounts are between 0.5 and 8 g oligomers and between 5 and 25 ghydrolysate. A total food of the invention may for instance contain atotal of 0.5 to 10.0 g of oligomers (preferred 1.0 to 8 g), and/or atotal of 2.5 to 50 g (preferred 5 to 25 g) of hydrolysate of theinvention. A infant formula of the invention may for instance contain atotal of 0.5 to 10.0 g (preferred 1.0 to 8.0 g) of oligomers, and/or atotal of 1 to 20 g (preferred 2.0 to 16.0 g) of the hydrolysate of theinvention.

[0057] The nutritional compositions of the invention can be used toprevent or treat any of a number of disorders of the gastrointestinaltract, and/or reduce or alleviate the symptoms of such disorders. Thesedisorders include, but not limited to infectious diarrhoea, traveller'sdiarrhoea, antibiotic-associated diarrhoea. The compositions of theinvention are particularly suited for the prevention of infectiousdiarrhoea caused by micro-organisms such as E. coli or Shigella, as mayoccur during travel and/or after treatment with antibiotics.

[0058] For these and other applications, the oligomers provide thefollowing effects and advantages:

[0059] they reduce and/or prevent of the adhesion of pathogens such asE. coli (HEC) and Shigella to the (wall of) the gastrointestinal tract,and in particular the intestinal wall; this reduces the risk ofinfection;

[0060] they promote the natural flora in the gastrointestinal tract andthereby reduce or prevent the growth of pathogens;

[0061] they promote and/or restore normal digestion and a properelectrolyte balance in the gastrointestinal tract.

[0062] In these and other applications, some further advantages of theuse of the oligomers include:

[0063] they stimulate growth of species of bifidobacteria which are notstimulated by e.g. TOS, which is also considered as a prebiotic;

[0064] the fermentation of the oligomers of the invention may improvethe absorption from calcium from the colon;

[0065] the oligomers have a viscosity which makes them particularlysuited for the preparation of food for administration into the stomachby tube or catheter.

[0066] In a further aspect, the invention therefore relates to the useof at least one oligomer, and/or of an hydrolysate containing at leastone oligomer as described above, in (the preparation of) a nutritionalcomposition for the prevention and/or treatment of disorders of thegastrointestinal tract, such as disorders listed above, in particularfor the prevention and/or treatment of diarrhoea, and in particularinfectious diarrhoea.

[0067] The invention also relates to the use of at least one oligomer,and/or of an hydrolysate containing at least one oligomer as describedabove, in (the preparation of) a nutritional composition for reducingand/or preventing the adhesion and/or the growth of undesiredmicro-organisms such as pathogens to the (wall of) the gastrointestinaltract.

[0068] Also, in a further aspect, the invention also relates to the useof at least one oligomer, and/or of an hydrolysate containing at leastone oligomer as described above, in (the preparation of) a nutritionalcomposition for promoting or restoring the natural intestinal flora,and/or for preventing or reducing a disturbance of the naturalintestinal flora.

[0069] Although the oligomers of the invention most preferably have adegree of polymerisation of 2-20, it should be clear that somehealth-promoting action may also be provided by oligomers of the generaltype, but with a somewhat larger degree of polymerisation, e.g. in theregion of 21-30. Thus, although not preferred, the use of minor amountsof such oligomers, if it results in a health promoting action asdescribed herein, should be considered equivalent to the embodimentsdescribed above.

EXAMPLES Example 1 Production of Arabiizo-oligosacchiarides

[0070] Commercial sugar beet fibre (Atlantis series 2025) containing 80%dietary fibre, about half of which is soluble, contains about 39%arabinose (determined using HPAEC after TFA hydrolysis). The fibre isdissolved in acetate buffer (50 mM, pH 5) and is incubated at 40° C.with an endo-arabinase, e.g as present in commercial enzyme preparationUltra SP (Novo Nordisk). After the incubation period, the reaction isstopped using a heating step (100° C.). The product is spray-dried andcontains about 10% of monomer (largely arabinose), 20% ofarabino-oligosaccharides (DP 2-6), 10% other oligosaccharides (DP 2-20),10% soluble fibre (DP >20) and 50% insoluble fibre (DP>20).

Example 2 Productioni of Arabino-oligosaccharides

[0071] Arabinan (Megazyme, 50% arabinose in polymer form) was incubatedwith Ultra SP (10 μl) for 3 h at 40° C. and pH 5. After deactivation ofthe enzyme, the product was freeze-dried and analysed using HPAEC. After3 h of incubation, the carbohydrate fraction consisted of about 25% ofmonomer, 40% of arabino-oligosaccharides (DP 2-20), 10% otheroligosaccharides (containing no arabinoses) and 25% of material having aDP above 20. After filtration over a 0.1 mm filter, the sterile liquidis spray-dried.

Example 3 Anti-adhtesive Effect

[0072] Different oligosaccharides obtained by hydrolysis of fibres wereused to measure inhibition of pathogen binding to human colon cancercells. Cells for the binding experiment are grown under standardconditions. The growth medium is removed from the cells and 0.2 ml ofrninnmal essential medium, 0.4 ml EHEC solution (2×10⁸ cfu/ml) and 0.4ml of test solution (5-10 mg/ml hydrolysed fibre) is added. Appropriateblanks are used as controls. Cells are incubated for an hour at 37° C.,after which the medium is removed. The cells are washed five times withPBS buffer, lysed, homogenised, diluted and plated to countcolony-forming units, following standard procedures. Comparison of theamount of cfu's found with the blank and with one of the fractions, theinhibiting power of the fraction can be calculated as percentagereduction in binding. The table below summarises results of bindingreduction. The results show that arabinose-containing oligosaccharidesreduce the binding of EHEC to Caco2 cells better than any of the otheroligosaccharides. Especially arabino-oligosaccharides shows very highbinding reduction capacity but also arabinoxylo- andarabinogalacto-oligosaccharides show more that 60% reduction in binding.All other oligosaccharides (non arabinose-containing) have lower than60% binding reduction activity. oligosaccharide % binding reductionarabinan 91 arabinoxylan 75 arabinogalactan 63 galactan 52 xylan 3galactomannan 24 galacturonan 21 lactose 28

Example 4 Bifidogenic Effect

[0073] Hydrolysed arabans (DP 2-9, containing about 10% monomer) fromsugar beet (see example 3) stimulate the growth of Bifidobacteriumstrains: lactis, infantis, angulatum and pseudocatelulatum.

[0074] When 150 mg of specific oligosaccharides is added to 5 g faeces,the growth of bifidobacteria increases. When the oligosaccharides aretrans-galacto-oligosaccharides, the bifidobacteria content increaseswith 5%. When the oligosaccharides are arabino-galactans, the numberincreases by about 38% toe over the same time period. When arabinoseoligomers are used, the increase is about 68%.

Example 5 Nutritional Composition

[0075] An infant formula is prepared by mixing the following components.Component g per 100 ml Protein equivalents 1.40 Casein 0.60 Whey protein0.80 Carbohydrates 7.0 Lactose 1.3 Glucose 0.2 Maltose 2.1Polysaccharides 3.5 Lipids 3.6 Saturated 1.4 Mono-unsaturated 1.7Poly-unsaturated 0.5 Arabino-oligosaccharides according to example 1 0.1

[0076] Further components: minerals, trace elements and vitamins inamounts as recommended by the EEC regulation 321.

Example 6 Supplement for the Treatnent of Diarrhoea

[0077] The product of example 2 (10 kg dry weight), glucose (20 kg),potassium citrate (2.9 kg) and sodium chloride (3.2 kg) are dissolved inwater to a total of 1000 1 in a tank to produce a liquid.

Example 7 Supplement for Enhancing Intestinal Function

[0078] A mixture of 2 g of hydrolysed arabinoxylans, 2 g offructo-oligosaccharides, 2 g of soy polysaccharides, 1 g of a probioticpreparation containing about 10¹⁰ freeze-dried lacto-bacillus cells, 5 gmaltodextrs and flavourings is prepared as a daily dosage form of 12 gpackaged in sachets. It improves the intestinal function.

1. A nutritional composition in individual single or multiple dailydosage form, containing non-digestible oligosaccharides, saidoligosaccharides comprising, per daily dosage, 0.3-10 g ofnon-digestible oligosaccharides containing at least one terminalarabinose unit.
 2. A nutritional composition according to claim 1,furthermore comprising, per daily dosage, 0.5-10 g of other nongestibleoligosaccharides selected from fructo-oligosaccharides,galacto-oligosaccharides, xylo-oligosaccharides andmanno-oligosaccharides.
 3. A complete food composition containingproteins (4-35 wt. %), lipids (4-35 wt. %), and digestible carbohydrates(30-90 wt. %), said composition containing, on a dry weight basis,0.07-6% of non-digestible oligosaccharides containing at least oneterminal arabinose unit.
 4. A complete food composition according toclaim 3, which is a liquid tube-feed composition containing, on a dryweight basis, 0.07-2.5% of non-digestible oligosaecharides containing atleast one tenrinal arabinose unit.
 5. A complete food compositionaccording to claim 3, which is a infant formula containing, on a dryweight basis, 0.15-6% of oligosaccharides containing at least oneterminal arabinose unit.
 6. A nutritional supplement containing, on adry weight basis, (1) 1-90% of non-digestible oligosaecharidescontaining at least one terminal arabinose unit, (2) 0-50% of othernon-digestible oligosaccharides, (3) 2-50% of non-digestiblepolysaceharides, the total of (1), (2) and (3) being at least 20%, and(4) 4-80% of digestible carbohydrates.
 7. A nutritional supplementaccording to claim 6, futher containing 10⁷ of probiotic micro-organismsper daily dosage form.
 8. Use of oligosaccharides containing at leastone terminal arabinose unit, in preparing a nutritional composition forthe prevention and treatment of adhesion of pathogenic micro-organismsto the intestinal wall, and/or for the enhancement of bifidogenicmicro-organisms in the intestinal tract.
 9. Use according to claim 8,wherein said arabinose-containing oligosaccharides are part of thefollowing mixture of nonigestible saccharides: (a) 10-100% (by weight)of said arabinose-containing oligosaccharides; (b) 0-50% of otheroligosaccharides; (c) 0-50% of monosaccharides; (d) 0-70% ofpolysaccharides.
 10. Use according to claim 9, wherein saidarabinose-containing oligosaccharides are part of the following mixtureof nondigestible saccharides: (a) 20-80% (by weight) of saidarabinose-containing oligosaccharides; (b) 10-50% of otheroligosaccharides; (c) 2-40% of monosaccharides; (d) 10-60% ofpolysacchaides.
 11. Use according to any one of claims 8-10, whereinsaid arabinose-containing oligosaccharides comprise at least 50%oligosaccharides containing at least two terminal arabinose units.
 12. Asaccharide mixture obtained by enzymatic hydrolysis ofarabinose-containing polysaccharides, containing: (a) 20-80% (by weight)of arabinose-containing oligosaccharides; (b) 2-40% of othernon-digestible oligosaccharides; (c) 2-40% of monosaccharides; and (d)10-60% of non-digestible polysaccharides.
 13. A saccharide mixtureaccording to claim 12, containing: (a) 35-75% (by weight) ofarabinose-containing oligosaccharides; (b) 5-30% of other non-digestibleoligosaccharides; (c) 5-30% of monosaccharides; and (d) 15-35% ofnon-digestible polysacchaides.